P928: REAL-LIFE ANALYSIS OF THE MULTIPLE MYELOMA PATIENT’S SURVIVAL IN A LARGE COHORT OF PATIENTS
Authors: N. Lopez-Muñoz, G. Hernandez-Ibarburu, J. M. Sánchez-Pina, R. A. Alonso, C. Cuellar, M. Calbacho, R. Ayala, R. Iñiguez, N. García Barrio, E. Vera, D. Pérez-Rey, L. Meloni, M. Pedrera-Jiménez, P. Serrano-Balazote, J. De La Cruz, J. Martínez-López
Journal: HemaSphere (2022)

Background: Multiple myeloma (MM) constitutes approximately 10% of hematological malignancies, with a median age at diagnosis of 65 years. Patient survival has improved considerably over the last 20 years with the introduction of new drugs. In 1999, the first immunomodulatory drug, thalidomide, was approved, followed by lenalidomide in 2005. In 2003, proteosome inhibitors such as bortezomib were introduced and, in 2015, anti-CD38 monoclonal antibodies such as daratumumab. Aims: By relying on the TriNetx platform, a global health research platform, we have analyzed the impact on the outcome of the introduction new drugs for MM in the last 20 years. We also analyzed the difference patterns of treatments between networks. Methods: First, we retrospectively selected patients diagnosed with symptomatic multiple myeloma between 1999 and 2019 in a tertiary care hospital in Spain, Hospital 12 de Octubre (H12O) in Madrid. Then, we analyzed data from more than 7500 patients diagnosed with CML from research networks: EMEA and the US; covering more than 16 million subjects. We compared the time of survival since the MM diagnosis in three groups depending of the age at MM diagnosis (less than 65, between 65 and 75, and more than 75 years old) over three periods of time: 1999-2009, 2010-2014 and 2015-2019 (2020 was excluded because of pandemic impact). Kaplan-Meier analysis was used for analyzing overall survival (OS) and differences between groups were tested for statistical significance using the log-rank test. Also, we analyzed the patterns of treatment along this time. Results: Approximately, a total 760 patients were included in the study. In the H12O, median OS was 45.1, 45.2, 65.1 months and not reached for the 1999-2009, 2010-2014 and 2015-2019 periods, respectively (p=0.001). Among the group of patients younger than 65 years old, the median OS was 64 months (47.5-81.4; 95%) among patients diagnosed in the period 1999-2009; 80 months (36.1-124; 95%) in 2010-2014; and median not reached for the 2014-2019 (p<.001). Similar results were found in a US cohort, including approximately 7000 patients, between the years 2010-2014 vs 2014-2019 (59.71% vs 64.20%, p<0.0001, HR 1.154 (1.074- 1.241) (figure 1). The same results were observed for the 65-75 years cohort, median OS was 62.6 months (50.9-74.3; 95%) for the 1999-2009 period, 70.6 months (33.1-108.1; 95%) between 2010 and 2014, and not reached for the 2014-2019 period (p<.001). The same occurs among more than 3000 patients from the US base between the years 2010-2014 vs 2014-2019 (53.96% vs 57.73%, p=0.016, HR 1.099 (1.018 - 1.187) (figure 2). Otherwise, patients older than 75 years have a median OS of 31.1 months and do not show a statistically significant difference regardless on the year of MM diagnosis (p=.18). Nor were clinically significant results obtained between the EMEA and US cohorts. On the other hand, the first-line treatment used in patients was analysed, and in both the EMEA and US cohorts, the use of bortezomib (46% vs 47% in the EMEA cohort; 62% vs 70% in US cohort), lenalidomide (43% vs 57% in EMEA cohort, 15% vs 18% in US cohort) and daratumumab (0% vs 4% in EMEA cohort, 2% vs 4% in US cohort) increases over the years comparing the 2010-2014 vs 2015-2019 time cohorts. This could explain the improved survival in more recent times. Summary/Conclusion: The introduction of new agents for the treatment of MM has transformed the natural history of the disease, achieving long survival times in younger patients. Thus, it is essential to continue to advance and develop new therapies.